Lee M, Sehatpour P, Hoptman M J, Lakatos P, Dias E C, Kantrowitz J T, Martinez A M, Javitt D C
Division of Experimental Therapeutics, Department of Psychiatry, Columbia University, New York, NY, USA.
Schizophrenia Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
Mol Psychiatry. 2017 Nov;22(11):1585-1593. doi: 10.1038/mp.2017.3. Epub 2017 Feb 7.
Schizophrenia is associated with cognitive deficits that reflect impaired cortical information processing. Mismatch negativity (MMN) indexes pre-attentive information processing dysfunction at the level of primary auditory cortex. This study investigates mechanisms underlying MMN impairments in schizophrenia using event-related potential, event-related spectral decomposition (ERSP) and resting state functional connectivity (rsfcMRI) approaches. For this study, MMN data to frequency, intensity and duration-deviants were analyzed from 69 schizophrenia patients and 38 healthy controls. rsfcMRI was obtained from a subsample of 38 patients and 23 controls. As expected, schizophrenia patients showed highly significant, large effect size (P=0.0004, d=1.0) deficits in MMN generation across deviant types. In ERSP analyses, responses to deviants occurred primarily the theta (4-7 Hz) frequency range consistent with distributed corticocortical processing, whereas responses to standards occurred primarily in alpha (8-12 Hz) range consistent with known frequencies of thalamocortical activation. Independent deficits in schizophrenia were observed in both the theta response to deviants (P=0.021) and the alpha-response to standards (P=0.003). At the single-trial level, differential patterns of response were observed for frequency vs duration/intensity deviants, along with At the network level, MMN deficits engaged canonical somatomotor, ventral attention and default networks, with a differential pattern of engagement across deviant types (P<0.0001). Findings indicate that deficits in thalamocortical, as well as corticocortical, connectivity contribute to auditory dysfunction in schizophrenia. In addition, differences in ERSP and rsfcMRI profiles across deviant types suggest potential differential engagement of underlying generator mechanisms.
精神分裂症与反映皮质信息处理受损的认知缺陷有关。失配负波(MMN)在初级听觉皮层水平上指示前注意信息处理功能障碍。本研究使用事件相关电位、事件相关频谱分解(ERSP)和静息态功能连接(rsfcMRI)方法,研究精神分裂症患者MMN损伤的潜在机制。在本研究中,分析了69例精神分裂症患者和38名健康对照者对频率、强度和持续时间偏差刺激的MMN数据。rsfcMRI数据来自38例患者和23名对照者的子样本。正如预期的那样,精神分裂症患者在不同类型偏差刺激下的MMN产生存在高度显著的、大效应量(P = 0.0004,d = 1.0)缺陷。在ERSP分析中,对偏差刺激的反应主要出现在与分布式皮质-皮质处理一致的θ(4 - 7Hz)频率范围内,而对标准刺激的反应主要出现在与丘脑-皮质激活的已知频率一致的α(8 - 12Hz)范围内。在精神分裂症患者中,观察到对偏差刺激的θ反应(P = 0.021)和对标准刺激的α反应(P = 0.003)均存在独立缺陷。在单试次水平上,观察到频率偏差与持续时间/强度偏差刺激的反应模式不同,以及在网络水平上,MMN缺陷涉及典型的躯体运动、腹侧注意和默认网络,不同类型偏差刺激的参与模式存在差异(P < 0.0001)。研究结果表明,丘脑-皮质以及皮质-皮质连接的缺陷导致了精神分裂症患者的听觉功能障碍。此外,不同类型偏差刺激下ERSP和rsfcMRI特征的差异表明潜在的产生机制存在不同程度的参与。